Polysensory interactions in the cuneate nucleus

1. The effects of light flashes or sound clicks on somatic sensory activity in the cuneate nucleus of the cat were studied. Polysensory interactions were demonstrated by means of gross potential recording in the cuneate nucleus or medial lemniscus, single unit recording in the cuneate nucleus, and excitability testing of tract terminals.

2. Brief flashes or clicks were found to produce negative (N) and positive (P) waves in the cuneate nucleus similar to those produced by cutaneous stimulation. Furthermore, the P wave evoked by conditioning photic or acoustic stimuli depressed the P wave produced by cutaneous test stimuli.

3. Conditioning photic or acoustic stimuli inhibited spontaneously firing cuneate neurones as well as those driven by cutaneous test stimuli.

4. Conditioning photic or acoustic stimuli depressed the test discharge in the medial lemniscus evoked by cutaneous test stimuli.

5. Micro-electrode stimulation within the cuneate nucleus evoked an antidromic response in the superficial radial nerve consisting of two spike complexes. Conditioning photic or acoustic stimuli caused an increase in the size of the initial spike complex and a depression in the secondary spike complex. These changes and the time courses of all the interactions observed were suggestive of presynaptic inhibition.

6. The modulatory influences of photic and acoustic stimuli on the cuneate nucleus were present under α-chloralose or pentobarbitone anaesthesia and the acoustic influence persisted after midcollicular decerebration. When added to other evidence, the above findings suggest that the reticular formation of the brain stem plays an important role in these polysensory interactions.

     

Intra-abdominal hypertension and abdominal compartment syndrome in burn patients

BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are known to occur in patients after major abdominal surgery. The incidence of IAH and ACS in the burn population is not known. METHODS: We prospectively recorded the intra-abdominal pressures of major burn patients admitted to our burn center from February 1999 to September 1999. A bladder pressure greater than 25 mm Hg was diagnosed as IAH. ACS was diagnosed when pulmonary compliance decreased in association with persistent IAH and was treated with abdominal decompression. RESULTS: Ten patients were placed on the protocol; of these, seven developed IAH. Five responded to conservative treatment. Two patients with 80% body surface area burns developed ACS and required decompression. CONCLUSIONS: IAH occurs commonly in major burn patients, and ACS is seen regularly in patients with more than 70% body surface area burns. We recommend bladder pressure measurements after infusion of more than 0.25 L/kg during the acute resuscitation phase and for peak inspiratory pressures greater than 40 cm H2O. Whereas ACS warrants surgical decompression of the abdominal cavity, IAH usually responds to conservative therapy.     

Spontaneous delta- to beta-globin switching in K562 human leukemia cells.

Previous analysis of the hemoglobin phenotype of the K562 human erythroleukemia cell line showed regulated expression of the epsilon-, zeta-, gamma-, alpha-, and delta-globin genes. Expression of the beta-globin genes has not been previously detected in this cell line. In this report, we describe the isolation of a variant of the K562 cell line that actively expresses beta-globin messenger RNA (mRNA) and polypeptide and shows greatly reduced expression of the delta-globin genes. This phenotype developed spontaneously in culture while two other K562 isolates grown under the same culture conditions have not undergone the same delta- to beta-globin switch. Analysis of this unique K562 variant shows that a construct containing a beta-globin promoter is quite active upon transient transfection into these cells. This finding suggests that the activation of the endogenous beta-globin genes results from changes in the trans-acting environment of these cells. The regulation of the beta-globin genes in this variant is characterized by a paradoxical decrease in the level of beta-globin mRNA after exposure to hemin. Other globin genes of this variant are appropriately regulated and show increased expression after hemin induction. Further study of this variant may shed light on mechanisms of gene regulation that are involved in hemoglobin switching.     

Targeting stathmin in prostate cancer

Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin is expressed at high levels in a variety of human cancers and provides an attractive molecule to target in cancer therapies that disrupt the mitotic apparatus. We developed replication-deficient bicistronic adenoviral vectors that coexpress green fluorescent protein and ribozymes that target stathmin mRNA. The therapeutic potential of these recombinant adenoviruses was tested in an experimental androgen-independent LNCaP prostate cancer model. Adenovirus-mediated transfer of anti-stathmin ribozymes resulted in efficient transduction and marked inhibition of stathmin expression in these cells. Cells that were transduced with the anti-stathmin adenoviruses showed a dramatic dose-dependent growth inhibition. This was associated with accumulation of LNCaP cells in the G2-M phases of the cell cycle. A similar dose-dependent inhibition of clonogenic potential was also observed in cells infected with anti-stathmin adenoviruses. Morphologic and biochemical analysis of infected cells showed a marked increase in apoptosis characterized by detachment of the cells, increased chromatin condensation, activation of caspase-3, and fragmentation of internucleosomal DNA. If these findings are confirmed in vivo, it may provide an effective approach for the treatment of prostate cancer.     

Practice patterns of antiphospholipid syndrome at a tertiary teaching hospital in Lebanon

The objective of the study was to describe the practice patterns of the antiphospholipid syndrome (APS) as compared with consensus guidelines for diagnosis and to determine whether practice patterns correlate with patient demographics and physician specialty. A retrospective medical chart review was conducted at the American University Hospital, in Beirut, Lebanon. All adult and pediatric patients admitted to the hospital between 1 January and 31 December 1998 who underwent either anticardiolipin antibodies (aCL) or lupus anticoagulant (LA) testing were included in the study. Work-up of APS syndrome was compared with: (a) the consensus guidelines for clinical diagnosis; (b) physician specialty; and (c) patient demographics (age, gender, ethnicity, health insurance status). Eighty-seven patients fulfilled at least one clinical criterion for APS; 92% were for work-up of thrombosis and 8% for pregnancy morbidities. Fifty-one percent underwent both aCL and LA. Overall 38% (33) of patients had an abnormal test result, however only 18% (6) underwent retesting, of whom only two satisfied a minimum of 6 weeks between test and retest TheAPS diagnostic work-up was requested by 11 different specialties. Rheumatologists were the most consistent in asking for both tests. APS is seen and diagnosed by a variety of medical specialties. Practice patterns as compared with the latest consensus are sub-optimal, and need to be improved. Interventions to help improve this have been discussed and are being implemented.     

Moyamoya syndrome with intraventricular hemorrhage in an adult with factor V Leiden mutation

OBJECTIVE: To report a case of proximal occlusion of 2 major cerebral vessels associated with moyamoya network circulation that manifested by spontaneous intraventricular hemorrhage. DESIGN: Case report. PATIENT AND RESULTS: A 36-year-old Syrian man presented with symptoms of sudden-onset headache, neck stiffness, and confusion. The computed tomography scan of his brain showed intraventricular bleeding, and the subsequent 4 vessel angiographies revealed occlusion of the left middle and anterior cerebral arteries with moyamoya appearance in the terminal branches. The coagulation profile showed the presence of heterozygous factor V Leiden mutation. The patient was treated conservatively until resolution of his blood clot, and later he was started on oral anticoagulation. CONCLUSION: Factor V Leiden mutation may cause large cerebral vessel occlusion with moyamoya syndrome in adults.     

Continuous perfusion with morphine of the orbitofrontal cortex reduces allodynia and hyperalgesia in a rat model for mononeuropathy

Recent imaging reports demonstrate the activation of the orbitofrontal cortical (OFC) area during acute and chronic pain. The aim of this study was to compare the effects of chronic perfusion of this area with morphine on nociception in control rats and in rats subjected to mononeuropathy. Chronic perfusion of morphine, using miniosmotic pumps, produced significant and naloxone-reversible depression of tactile and cold allodynias and thermal hyperalgesia, observed in neuropathic rats, while it produced significant elevation and naloxone insensitive increase of acute nociceptive thresholds in control rats. The observed results support the idea that this area is a component of a flexible cerebral network involved in pain processing and perception.     

Chronic thalamotomy increases pain-related behavior in rats

The thalamus has been traditionally considered as the 'chief organ' by which pain is perceived (Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain 1911;34:102-254). However, several clinical and experimental observations led to a challenge of this traditional view. In this report, we demonstrate that chronic thalamic lesions, instead of producing hypoalgesia, increased pain reactivity in rats. Different groups of rats were subjected to either subtotal, lateral or medial thalamic lesions. Their reactions to nociceptive stimuli were then assessed for a period of 1-2 months. Rats in the different groups showed an increased reactivity to acute mechanical and thermal nociceptive stimuli and an increase in the pain scores of the formalin test. These results suggest an important role of the thalamus in pain modulation in addition to that of nociceptive transmission.